研究组在美国《分子精神病学》发表题为“Dentate gyrus-CA3 glutamate release/NMDA transmission mediates behavioral despair and antidepressant-like responses to leptin”的文章。
Molecular Psychiatry advance online publication, 5 August 2014; doi:10.1038/mp.2014.75
Dentate gyrus-CA3 glutamate release/NMDA transmission mediates behavioral despair and antidepressant-like responses to leptin.
X Wang1,2, D Zhang2 and X-Y Lu2
Institute for Metabolic and Neuropsychiatric Disorders, Binzhou Medical University Hospital, Binzhou, China and 2Department of Pharmacology, The University of Texas Health
Science Center at San Antonio, San Antonio, TX, USA. Correspondence: Dr X-Y Lu, Department of Pharmacology, The University of Texas Health Science Center at San Antonio,
7703 Floyd Curl Drive, San Antonio, TX 78229, USA.
Compelling evidence supports the important role of the glutamatergic system in the pathophysiology of major depression and also as a target for rapid-acting antidepressants. However, the functional role of?glutamate?release/transmission?inbehavioral?processes related to depression and antidepressant efficacy remains to be elucidated. In this study,?glutamaterelease?and?behavioral?responses?to tail suspension, a procedure commonly used for inducing?behavioral?despair, were simultaneously monitored in real time. The onset of tail suspension stress evoked a rapid increase in?glutamate?release?in hippocampal field CA3, which declined gradually after its offset. Blockade of N-methyl-D-aspartic acid (NMDA) receptors by intra-CA3 infusion of MK-801, a non-competitive?NMDA?receptor antagonist, reversed?behavioral?despair. A subpopulation of granule neurons that innervated the CA3 region expressed?leptin?receptors and these cells were not activated by stress.Leptin?treatment dampened tail suspension-evoked?glutamate?release?in CA3. On the other hand, intra-CA3 infusion of?NMDAblocked the?antidepressant-like?effect of?leptin?in reversing?behavioral?despair?in both the tail suspension and forced swim tests, which involved activation of Akt signaling in DG. Taken together, these results suggest that the DG-CA3 glutamatergic pathway is critical for mediating?behavioral?despair?and?antidepressant-like?responses?to?leptin.Molecular Psychiatry advance online publication, 5 August 2014; doi:10.1038/mp.2014.75.